POS0785 EXPRESSION OF MYXOVIRUS RESISTANCE PROTEIN A IN LUPUS NEPHRITIS
Authors: L. Liu, K. De Leeuw, G. Diercks, C. Stegeman, B. Doornbos- van der Meer, H. Van Goor, M. Heuvel, J. Westra
Journal: Annals of the Rheumatic Diseases (2022)

Background Lupus nephritis (LN) is regarded as one of the most severe organ manifestations of systemic lupus erythematosus (SLE) [1]. It has been shown that type I interferons (IFN) are important cytokines in the pathogenesis of SLE and LN and could possibly serve as a histological marker for kidney lesions in LN [2]. However, the direct measurement of type I IFN protein in tissues has remained elusive. Myxovirus resistance protein A (MxA) which is upregulated by IFN-1, can easily be measured, and could be used as a potential biomarker. In addition, dendritic cells are main producers of IFN-1. Objectives To investigate the expression of MxA and CD303 which is a plasmacytoid dendritic cells (pDCs) specific marker [3] by immunohistochemical analysis of renal specimens obtained from LN patients and from patients with other types of nephritis. Methods LN was diagnosed based on the International Society of Nephrology/Renal Pathology Society (ISN/RPS) classification. In total, 41 renal tissue samples were collected from lupus nephritis including all classes (I-V according to ISN/RPS classification), and compared to 70 biopsies from other forms of nephritis. MxA was detected by immunohistochemistry staining. Scoring of MxA staining was done semi-quantitative for separate structures in nephritis tissues with a range from 0 to 3+. Scoring was based on the intensity of the staining, in which ‘0’ meant no expression; ‘1’: weak expression; ‘2’: moderate expression; and ‘3+’: strong expression. The expression of CD303 was measured by counting the number of CD303 positive cells in the glomerulus or in the tubular interstitium. Results The MxA average scores of the total LN group were higher than control specimens especially in distal tubules (Figure 1). The MxA expression in LN classes I, II, and V biopsies was mainly increased compared to tissues of patients with minimal change disease, mesangioproliferative nephritis, and membranous nephropathy (Figure 2a,2b,2d). However, MxA staining was comparable in LN classes III/IV compared to control groups (Figure 2c). The staining of CD303 showed that pDC are more present in tubular interstitium than in glomeruli. Furthermore, CD303-positive cells were highest in LN class IV, but overall numbers of pDCs were higher in controls groups compared to LN groups (Figure 3). Conclusion Our data indicate that MxA expression is higher in LN vs. other types of nephritis. These results suggest that MxA could be a potential additional histological marker to establish the diagnosis of lupus nephritis on the kidney biopsy. In contrast to the increased expression of MxA in LN, we found decreased numbers of pDCs. Therefore, it is important to investigate which other cells are the main producers of IFN-1 in further studies. References [1]Anders HJ, Saxena R, Zhao MH, et al. Lupus nephritis.[J]. Nat Rev Dis Primers. 2020;6(1):7. [2]Xue L, Liu L, Huang J, et al. Tumor Necrosis Factor-Like Weak Inducer of Apoptosis Activates Type I Interferon Signals in Lupus Nephritis.[J]. Biomed Res Int. 2017;2017:4927376. [3]Boiocchi L, Lonardi S, Vermi W, Fisogni S, Facchetti F. BDCA-2 (CD303): a highly specific marker for normal and neoplastic plasmacytoid dendritic cells. Blood 2013;122:296-7. Disclosure of Interests None declared